Cited by 694Cannabis and Cannabinoid ResearchAdipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and Obesity

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Activation of the Peripheral Endocannabinoid System in Human Obesity

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Engeli, Stefan, Böhnke, Jana, Feldpausch, Mareike, Gorzelniak, Kerstin, Janke, Jürgen, Bátkai, Sándor, Pacher, Pál, Harvey-White, Judy, Luft, Friedrich C., Sharma, Arya M., Jordan, Jens·2005·Diabetes

DOI 10.2337/diabetes.54.10.2838PMC PMC2228268

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Abstract

Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.

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Huang, L., Toyoshima, M., Asakawa, A., Inoue, K., Harada, K. H., Kinoshita, T., Chen, S., & Koizumi, A. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.10.003 · Cited by 4
Role of the Endocannabinoid System in Management of Patients with Type 2 Diabetes Mellitus and Cardiovascular Risk Factors
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Endocrine, metabolic, and endocannabinoid correlates of obesity in rats exhibiting high anxiety-related behaviors
Vega-Torres, J. D., Kalyan-Masih, P., Argueta, D. A., DiPatrizio, N. V., & Figueroa, J. D. (2019) · Matters Select · doi:10.19185/matters.201906000003 · Cited by 4
“For example, endocannabinoid levels increase in the upper small-intestinal epithelium of rodents after tasting dietary lipids [26] [27], fasting [28] [29] [30], and are elevated in blood in rodent and human diet-induced obesity [29] [31] [32] [33] [34].”
Background
Lower abdominal adipose tissue cannabinoid type 1 receptor availability in young men with overweight
Pekkarinen, L., Kantonen, T., Oikonen, V., Haaparanta‐Solin, M., Aarnio, R., Dickens, A. M., von Eyken, A., Latva‐Rasku, A., Dadson, P., Kirjavainen, A. K., et al. (2023) · Obesity · doi:10.1002/oby.23770 · Cited by 3
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Background
Higher plasma levels of endocannabinoids and analogues are correlated with a worse cardiometabolic profile in middle-aged adults
Rodríguez‐García, C., Osuna‐Prieto, F. J., Köhler, I., Sanchez-Gomez, J., Ruiz-Campos, S., Castillo, M. J., Amaro‐Gahete, F. J., Martínez‐Téllez, B., & Jurado‐Fasoli, L. (2024) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-024-01063-6 · Cited by 3
“Indeed, elevated circulating levels of 2-AG and AEA [15, 16] are associated with insulin resistance and visceral adiposity in individuals with overweight and obesity [17–19].”
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The Endocannabinoid Network: Insight Into the Regulation of the Neuroendocrine and Metabolic Systems
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Endocannabinoid system and cardio-metabolic risk.
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Endocannabinoid System and Pathophysiology of Adipogenesis: Current Management of Obesity
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Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis UsersPreprint
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Sistema endocanabinoide y desarrollo de esteatosis hepática
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Plasma Endocannabinoids Are Independently Associated With the Metabolic Function of White Adipose Tissue
Dion, D., Noll, C., Fortin, M., Haroune, L., Saibi, S., Sarret, P., & Carpentier, A. C. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae657 · Cited by 2
“Circulating 2-AG and/or AEA are increased in patients with obesity or type 2 diabetes, and these increases are associated with markers of obesity and metabolic syndrome such as BMI, waist circumference, visceral fat mass, insulin resistance, TGs, and NEFAs (18, 31, 32, 40, 41).”
Cannabidiol oil delays pancreatic islet dysfunction in Wistar rats under hypercaloric diet
Cortes-Justo, E., Ortiz-Butrón, R., & Vilches‐Flores, A. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.117993 · Cited by 2
Anandamide and Other Acylethanolamides
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“Se ha sugerido que el estado de hiperactividad cannabinoide puede explicar las recaídas en la obesidad (Engeli et al. 2005).”
Background
Endocannabinoids and Energy Homeostasis
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“White adipocytes express CB1 receptors (16,17, 20 ), and in vitro experiments demonstrate that the CB1 agonist WIN-55,212 stimulates adipocyte differentiation and increases the activity of lipoprotein lipase; both actions are blocked by pretreatment with SR 141716 (16).”
BackgroundResult
Rimonabant-Induced Persistent Vomiting
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Endocannabinoids: the lipid effectors of metabolic regulation in health and disease
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The Effect of Endocannabinoid System on Energy Metabolism and Obesity
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Endocannabinoid Metabolism in Posttraumatic Stress Disorder: Results From a Neuroimaging Study With the Novel Fatty Acid Amide Hydrolase Probe, [C-11] Curb
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Modulation of Endocannabinoids by Caloric Restriction Is Conserved in Mice but Is Not Required for Protection from Acute Kidney Injury
Hoyer-Allo, K. J. R., Späth, M. R., Hanßen, R., Johnsen, M., Brodesser, S., Kaufmann, K., Kiefer, K., Koehler, F. C., Göbel, H., Kubacki, T., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115485 · Cited by 2
Alterations in the Endocannabinoid System as a Link Between Unbalanced Energy Homeostasis, Neuroinflammation, and Neurological and Neuropsychiatric Disorders
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Endokannabinoidnaya sistema: struktura i potentsial'nye vozmozhnosti v regulyatsii massy tela
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Endocannabinoid system and eating behavior / Sistema endocannabinoide y conducta alimentaria
Ramı́rez-Emiliano, J., Ortega-Barrón, I. G., Caudillo-Ortega, N. A., Negrete‐Díaz, J. V., & Pérez‐Vázquez, V. (2024) · Revista Mexicana de Trastornos Alimentarios/Mexican Journal of Eating Disorders · doi:10.22201/fesi.20071523e.2024.1.707 · Cited by 1
Opioid peptides in the regulation of eating behavior and appetite. (A Narrative Review)
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The interplay of leptin and the peripheral endocannabinoid system in energy homeostasis and obesity, Modulation by linoleic acid and exercise
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Circulating endocannabinoids and brain anatomy: unraveling the weight loss connection through lifestyle and surgery approaches
St‐Arnaud, G., Rocheleau, T., Veilleux, A., Rakotoarivelo, V., & Marzo, V. D. (2025) · Exploration of Endocrine and Metabolic Diseases · doi:10.37349/eemd.2025.101427 · Cited by 1
Effects of different ratio of sweet sorghum silage to corn silage diets on serum metabolome of lactating dairy cows
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“Engeli et al. (2005) found that circulating levels of anandamide (AEA) and 1/2-AG were increased by 35 and 52% in the obese and lean women, respectively.”
Dietary Manganese Modulates Microbiota and Intestinal N ‐Acylethanolamines in a Sex‐Specific Manner in Mice With Diet‐Induced Obesity
Agudelo, F. A. G., Leblanc, N., Bourdeau‐Julien, I., St‐Arnaud, G., Dahhani, F., Flamand, N., Veilleux, A., Marzo, V. D., & Raymond, F. (2025) · The FASEB Journal · doi:10.1096/fj.202500934r · Cited by 1
“However, Mn intake has been reported to have beneficial effects in reversing metabolic dysfunction [38], and to be important in regulating blood lipid metabolism [39], which corresponds to the results we obtained here.”
Cannabinoid receptors as targets for drug discovery
Iliopoulos‐Tsoutsouvas, C., Iyer, M. R., & Makriyannis, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00052-2 · Cited by 1
Taurine attenuates lipid accumulation via the eCB-CB1 axis: evidence from adipose metabolomics in HFD-fed mice and 3D adipocyte spheroids
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Siebers, M. J., Canales-Romero, D., & Fuß, J. (2026) · The Neuroscientist · doi:10.1177/10738584261440907 · Cited by 1
“Adipose tissue constitutively produces eCBs, and its role in acute release during exercise is debated, especially since baseline levels of AEA and 2-AG tend to decrease after endurance training over several weeks (Engeli et al 2005; Siebers et al 2023; Di et al 2024).”
The Role of the Endocannabinoid System in the Pathogeny of Type 2 Diabetes
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“Although ECs influence numerous behaviors, in genral the net effect of ECs at diverse sites in the brain and hroughout the body is anabolic, facilitating increased enrgy intake, decreased energy expenditure, and increased ccumulation of body fat.(2)”
Influential
Diagnostics of impaired glucose tolerance by the direct mass-spectrometric analysis of plasma metabolites
Lokhov, P. G., Trifonova, O. P., Maslov, D. L., Balashova, E. E., Archakov, A. I., Shestakova, E. A., Shestakova, M. V., & Dedov, I. I. (2014) · Problems of Endocrinology · doi:10.14341/probl20146034-9 · Cited by 1
THE ENDOCANNABINOID SYSTEM IN ADIPOSE TISSUE
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The Role of Endocannabinoid System in Menopause and Its Related-Diseases
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Implication of the endocannabidiome and metabolic pathways in fragile X syndrome pathophysiology
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“…acid (DPA, 22:5) Dihomo-γ -Linolenic Acid (DGLA, 20:3) Docosahexaenoic acid (DHA, 22:6) Arachidonic acid (AA or ARA, 20:4) Docosapentaenoic acid (DPA, 22:5) O. Dionne et al. patients with binge eating disorders and obese postmenopausal women (Engeli et al., 2005; Monteleone et al., 2005).”
Pharmacology of Non-Psychoactive Phytocannabinoids and Their Potential for Treatment of Cardiometabolic Disease
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“L’expression de ces récepteurs était plus importante dans les pré-adipocytes que dans les adipocytes matures [5] indiquant que l’activation du récepteur CB1 joue plus un rôle dans les processus métaboliques que dans la différenciation de l’adipocyte.”
Involvement of the Endocannabinoid System in Metabolism and Fertility
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Authors: Engeli, S., Böhnke, J., Feldpausch, M., Gorzelniak, K., Janke, J., Bátkai, S., Pacher, P., Harvey-White, J., Luft, F. C., Sharma, A. M., & Jordan, J.
Affiliations: Helios Hospital Berlin-Buch (DE)
Franz Volhard Clinical Research Center, Charité Campus Buch, and HELIOS Klinikum Berlin, Berlin, Germany
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Maryland
National Institutes of Health (US)
McMaster University (CA)
ORCID: Engeli, Stefan
Luft, Friedrich C.
Sharma, Arya M.
Jordan, Jens
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2005-10-01
Volume: 54
Issue: 10
Pages: 2838-2843
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.54.10.2838
PMC: PMC2228268
OpenAlex: W2162112945
Cited by: 686
References: 37
Citations by year: 2026: 11 · 2025: 14 · 2024: 20 · 2023: 19 · 2022: 20 · 2021: 30 · 2020: 29 · 2019: 24 · 2018: 30 · 2017: 30 · 2016: 15 · 2015: 31 · 2014: 29 · 2013: 29 · 2012: 33
FWCI: 38.06
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders: Sanofi
Bundesministerium für Bildung und Forschung
National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (Z01AA000375)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: obesity, cannabinoid type 1 receptor, fatty acid amide hydrolase, anandamide, 2-arachidonoylglycerol, adipose tissue, weight loss, human adipocytes, type 2 diabetes risk
MeSH terms: Fatty Acid Amide Hydrolases, Adipose Tissue, Amidohydrolases, Arachidonic Acids, Body Composition, Female, Glycerides, Humans, Middle Aged, Obesity, RNA, Messenger, Weight Loss, Gene Expression, Body Mass Index, Linear Models, Postmenopause, Reverse Transcriptase Polymerase Chain Reaction, Receptor, Cannabinoid, CB1, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids

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Activation of the Peripheral Endocannabinoid System in Human Obesity

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